Throughout this disclosure, various publications, patents and published patent specifications are referenced by an identifying citation. The disclosures of these publications, patents and published patent specifications are hereby incorporated by reference into the present disclosure to more fully describe the state of the art to which this invention pertains.
HIV infection continues to spread worldwide in both developed and underdeveloped countries with no effective vaccine available. Current antiretroviral drug therapies have been successful in suppressing viral infection as long as the patient is compliant with the prescribed regimen. However, with prolonged use, these treatments can become toxic and drug resistant viral escape mutants arise [1-5]. New and innovative therapies need to be developed that overcome the limitations of current small drug antiretrovirals. Gene therapy offers a promising alternative or supplement to current treatments due to advantages which include the possibility of a one-time treatment, controlled or constitutive anti-HIV gene expression, and long-term viral inhibition particularly if hematopoietic progenitor cells (HPCs) are targeted. Many anti-HIV genes have been evaluated for their efficacy in inhibiting viral infection including antisense RNAs, riboyzymes, RNA decoys, siRNAs, intrabodies, transdominant proteins, and restriction factors [8-23, 42-43]. These molecules have been targeted to both viral genes and proteins and also cellular genes critical for viral infection and replication. Several groups, including ours, have been involved with human clinical trials using a select number of these anti-HIV genes transferred into HPCs by retroviral and lentiviral vectors [19-23].
However, improvements in stem cell transduction efficiency and in the effectiveness of the vector to interfere with different stages of the HIV life cycle are still needed.
However, none of these prior art approaches have effectively eliminated HIV entry and replication in vivo. This invention satisfies this need and provides related advantages as well.